The Indiana Alzheimer Disease Center National Cell Repository was established to collect and maintain information and biological specimens on large numbers of genetically informative, phenotypically well-characterized families with multiple individuals affected with Alzheimer s Disease (AD). These pedigrees were then made available to researchers worldwide and have lead to our expanded understanding of the genetics of AD. During the past few years, the scope of research regarding familial dementias has broadened to include not only familial AD but also familial dementia of other etiological causes. While the molecular mechanism underlying several of these disorders has been elucidated, the pathogenesis of these neurodegenerative diseases remains unclear. Some intriguing similarities among the diseases have been found and it has been postulated that these overlaps between diseases represent shared pathogenic mechanisms. In response to the expanded scope of familial dementia research, the National Cell Repository proposes during the next five years to broaden its focus to include the ascertainment, characterization and distribution of pedigrees with all types of familial dementia. The National Cell Repository will continue to prioritize autopsy confirmation of disease. Since the commencement of the Repository, criteria for neuropathological diagnosis have evolved, making it essential that certain brain samples in the Repository receive further examination to confirm and further delineate the neuropathological diagnoses. To increase the usefulness of all families in the National Cell Repository, molecular testing of dementia-related causative genes (APP, PSI, PS2, Tau, PRNP) will be performed in early onset families with clinical findings consistent with the known genetic defects. In addition, APOE genotyping will be performed in all National Cell Repository samples to increase the value of these samples to researchers. Results of all molecular and neuropathological testing will be made available to AD investigators through the Cell Line and DNA Catalog. The National Cell Repository will continue to work with AD researchers to provide the most useful and informative data for genetic studies. This focus on high quality pedigree characterization has led the Repository to be used by nearly 50 researchers and has resulted in 40 publications.